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Archives of Virology
Published in: Archives of Virology 3/2015

01-03-2015 | Original Article

Recombinant influenza A virus hemagglutinin HA2 subunit protects mice against influenza A(H7N9) virus infection

Authors: Kelvin K. W. To, Anna J. X. Zhang, Andy S. F. Chan, Can Li, Jian-Piao Cai, Candy C. Y. Lau, Chuan-Gen Li, Akhee S. Jahan, Wai-Lan Wu, Lanjuan Li, Alan Ka-Lun Tsang, Kwok-Hung Chan, Honglin Chen, Kwok-Yung Yuen

Published in: Archives of Virology | Issue 3/2015

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Abstract

A novel avian influenza A(H7N9) virus has emerged to infect humans in eastern China since 2013. An effective vaccine is needed because of the high mortality despite antiviral treatment and intensive care. We sought to develop an effective vaccine for A(H7N9) virus. The HA2 subunit was chosen as the vaccine antigen because it is highly conserved among the human A(H7N9) virus strains. Moreover, in silico analysis predicted two immunogenic regions within the HA2 subunit that may contain potential human B-cell epitopes. The HA2 fragment was readily expressed in Escherichia coli. In BALB/c mice, intraperitoneal immunization with two doses of HA2 with imiquimod (2-dose-imiquimod) elicited the highest geometric mean titer (GMT) of anti-HA2 IgG (12699), which was greater than that of two doses of HA2 without imiquimod (2-dose-no-adjuvant) (6350), one dose of HA2 with imiquimod (1-dose-imiquimod) (2000) and one dose of HA2 without imiquimod (1-dose-no-adjuvant) (794). The titer of anti-HA2 IgG was significantly higher in the 1-dose-imiquimod group than the 1-dose-no-adjuvant group. Although both hemagglutination inhibition titers and microneutralization titers were below 10, serum from immunized mice showed neutralizing activity in a fluorescent focus microneutralization assay. In a viral challenge experiment, the 2-dose-imiquimod group had the best survival rate (100 %), followed by the 2-dose-no-adjuvant group (90 %), the 1-dose-imiquimod group (70 %) and the 1-dose-no-adjuvant group (40 %). The 2-dose-imiquimod group also had significantly lower mean pulmonary viral loads than the 1-dose-imiquimod, 1-dose-no-adjuvant and non-immunized groups. This recombinant A(H7N9)-HA2 vaccine should be investigated as a complement to egg- or cell-based live attenuated or subunit influenza vaccines.
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Metadata
Title
Recombinant influenza A virus hemagglutinin HA2 subunit protects mice against influenza A(H7N9) virus infection
Authors
Kelvin K. W. To
Anna J. X. Zhang
Andy S. F. Chan
Can Li
Jian-Piao Cai
Candy C. Y. Lau
Chuan-Gen Li
Akhee S. Jahan
Wai-Lan Wu
Lanjuan Li
Alan Ka-Lun Tsang
Kwok-Hung Chan
Honglin Chen
Kwok-Yung Yuen
Publication date
01-03-2015
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 3/2015
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-014-2314-x

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